Cell Models Core ? Project Summary The COBRE in Digestive & Liver Disease (CDLD) Cell Models Core will provide CDLD investigators with access to state-of-the-art tissue culture models of digestive and liver disease. We will use genome engineering technologies including CRIPSR-Cas9 to introduce specific genetic alterations into established cell lines and into induced pluripotent stem cells (iPSCs). The iPSCs will be differentiated to form cells of the gastrointestinal tract and liver that will be used for study by CDLD investigators. In addition to providing CDLD investigators cell lines and organoids that can be used for direct analyses, the Cell Models Core will also equip investigators with mentoring, training, and critical reagents allowing them to establish the procedures in their own laboratories. Through training opportunities, the Core will advance the technological toolbox of CDLD investigators, increase their competitiveness for funding, and enable them to advance as experts in digestive and liver disease research. The Core will also adopt a program of rigorous evaluation to ensuring optimal performance and continual access to new technologies as they are developed. The Cell Models Core represents a new core research resource at the Medical University of South Carolina. Currently, this technology is only available to a limited group of investigators and is temporarily run from the Duncan laboratory. Dr. Stephen A. Duncan, who will lead the core, is an expert in stem cell biology and cell differentiation, and he has used genome engineering extensively to generate cells to model liver disease. He has previous experience in running a similar core while a Professor at the Medical College of Wisconsin. The Core also recruited the expertise of Dr. Jorge Mnera who has pioneered the generation of colonic organoids from iPSCs. The Core leadership has already worked closely with the CDLD Junior Investigators to generate preliminary data for their proposed projects. Support through the COBRE will allow the Cell Models Core to expand its operation and provide these essential services to a broad community of CDLD investigators. A needs assessment survey ascertained that 21 established CDLD investigators and 3 junior investigators would use the core in the immediate future. The core will therefore have a substantial impact and advance digestive disease and liver research at MUSC.